Glucose starvation induces resistance to metformin through the elevation of mitochondrial multidrug resistance protein 1

Metformin, a drug for type 2 diabetes mellitus, has shown therapeutic effects for various cancers. However, it had no beneficial effects on the survival rate of human malignant mesothelioma (HMM) patients. The present study was performed to elucidate the underlying mechanism of metformin resistance in HMM cells. Glucose‐starved HMM cells had enhanced resistance to metformin, demonstrated by decreased apoptosis and autophagy and increased cell survival. These cells showed abnormalities in mitochondria, such as decreased ATP synthesis, morphological elongation, altered mitochondrial permeability transition pore and hyperpolarization of mitochondrial membrane potential (MMP). Intriguingly, Mdr1 was significantly upregulated in mitochondria but not in cell membrane. The upregulated mitochondrial Mdr1 was reversed by treatment with carbonyl cyanide m‐chlorophenyl hydrazone, an MMP depolarization inducer. Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment. The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy.     

‘I believe high blood pressure can kill me:’ using the PEN-3 Cultural Model to understand patients’ perceptions of an intervention to control hypertension in Ghana

Objectives: Currently in Ghana, there is an on-going task-shifting strategy in which nurses are trained in hypertension management. While this study will provide useful information on the viability of this approach, it is not clear how patients in the intervention perceive hypertension, the task-shifting strategy, and its effects on blood pressure management. The objective of this paper is to examine patients’ perceptions of hypertension and hypertension management in the context of an on-going task-shifting intervention to manage blood pressure control in Ghana.

Design: Forty-two patients participating in the Task Shifting Strategy for Hypertension program (23 males, 19 females, and mean age 61. 7 years) completed in-depth, qualitative interviews. Interviews were transcribed, and key words and phrases were extracted and coded using the PEN-3 Cultural Model as a guide through open and axial coding techniques, thus allowing rich exploration of the data.

Results: Emergent themes included patients’ perceptions of hypertension, which encompassed misperceptions of hypertension and blood pressure control. Additional themes included enablers and barriers to hypertension management, and how the intervention nurtured lifestyle change associated with blood pressure control. Primary enabling factors included the supportive nature of TASSH nurses, while notable barriers were financial constraints and difficulty accessing medication. Nurturing factors included the motivational interviewing and patient counseling which instilled confidence in the patients that they could make lasting behavior changes.

Conclusions: This study offers a unique perspective of blood pressure control by examining how patients view an on-going task-shifting initiative for hypertension management. The results of this study shed light on factors that can help and hinder individuals in low-resource settings with long-term blood pressure management.     

A systematic scoping review of environmental health conditions and hygiene behaviors in homeless shelters

Background

There are well-established relationships between health and homelessness, and shelters can facilitate the transmission of diseases and contribute to their prevention. Adequate environmental health conditions and hygiene behaviors in homeless shelters are fundamental to the health of their clients, a marginalized population. We report the status of environmental health conditions and hygiene behaviors in homeless shelters and associated health outcomes; interventions to improve these conditions, behaviors, and outcomes; and obstacles to improvement.

Pseudocystic pilomatricoma: A new variant and review of the literature

A classic pilomatricoma, which usually presents with an asymptomatic, solitary, firm, subcutaneous nodule in the head, neck, or extremities of the paediatric population, is easily diagnosed based on its characteristic clinical and histopathological features. However, its variants often pose particular diagnostic challenges to clinicians due to their rarity and diverse clinicopathological features. We present a new pseudocystic variant, manifesting as solid lesions floating in a fluid‐filled sac.     

Generalized,severe epidermolysis bullosa simplex caused by a Keratin 5 p.E477K mutation

Epidermolysis bullosa simplex (EBS) is a skin fragility disorder resulting from mutations of structural proteins in the epidermis. We provide a brief report of long‐term survival and reproduction in a mother with EBS due to keratin 5 (KRT5) c.1429G > A (p.E477K) mutation, which causes a particularly severe form of the disease.